Classifications

• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
  • A23P10/00—Shaping or working of foodstuffs characterised by the products
  • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
  • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
  • A61K9/1605—Excipients; Inactive ingredients
  • A61K9/1629—Organic macromolecular compounds
  • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
  • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
  • A61K9/1605—Excipients; Inactive ingredients
  • A61K9/1629—Organic macromolecular compounds
  • A61K9/1658—Proteins, e.g. albumin, gelatin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
  • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
  • A61K9/1605—Excipients; Inactive ingredients
  • A61K9/1664—Compounds of unknown constitution, e.g. material from plants or animals
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
  • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
  • A61K9/1682—Processes
  • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
  • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
  • A61K9/5005—Wall or coating material
  • A61K9/5021—Organic macromolecular compounds
  • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
  • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
  • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
  • A61K9/5005—Wall or coating material
  • A61K9/5063—Compounds of unknown constitution, e.g. material from plants or animals
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
  • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
  • A61K9/5089—Processes
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
  • B01J13/02—Making microcapsules or microballoons
  • B01J13/04—Making microcapsules or microballoons by physical processes, e.g. drying, spraying
  • B01J13/043—Drying and spraying
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
  • B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
  • B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
  • B01J2/04—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops in a gaseous medium
• • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
  • F26—DRYING
  • F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
  • F26B3/00—Drying solid materials or objects by processes involving the application of heat
  • F26B3/02—Drying solid materials or objects by processes involving the application of heat by convection, i.e. heat being conveyed from a heat source to the materials or objects to be dried by a gas or vapour, e.g. air
  • F26B3/06—Drying solid materials or objects by processes involving the application of heat by convection, i.e. heat being conveyed from a heat source to the materials or objects to be dried by a gas or vapour, e.g. air the gas or vapour flowing through the materials or objects to be dried
  • F26B3/08—Drying solid materials or objects by processes involving the application of heat by convection, i.e. heat being conveyed from a heat source to the materials or objects to be dried by a gas or vapour, e.g. air the gas or vapour flowing through the materials or objects to be dried so as to loosen them, e.g. to form a fluidised bed
• • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
  • F26—DRYING
  • F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
  • F26B3/00—Drying solid materials or objects by processes involving the application of heat
  • F26B3/02—Drying solid materials or objects by processes involving the application of heat by convection, i.e. heat being conveyed from a heat source to the materials or objects to be dried by a gas or vapour, e.g. air
  • F26B3/10—Drying solid materials or objects by processes involving the application of heat by convection, i.e. heat being conveyed from a heat source to the materials or objects to be dried by a gas or vapour, e.g. air the gas or vapour carrying the materials or objects to be dried with it
  • F26B3/12—Drying solid materials or objects by processes involving the application of heat by convection, i.e. heat being conveyed from a heat source to the materials or objects to be dried by a gas or vapour, e.g. air the gas or vapour carrying the materials or objects to be dried with it in the form of a spray, i.e. sprayed or dispersed emulsions or suspensions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
  • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
  • A61K2035/126—Immunoprotecting barriers, e.g. jackets, diffusion chambers
  • A61K2035/128—Immunoprotecting barriers, e.g. jackets, diffusion chambers capsules, e.g. microcapsules

Definitions

• the present invention is framed within the pharmaceutical, biomedical, agricultural, cosmetic and food sectors. More specifically, it describes an installation and a drying and / or encapsulation process of thermolabile substances such as probiotic functional ingredients, polyunsaturated fatty oils, antioxidants, etc.
• the spray drying technique consists in applying a counter-current of hot air to an aerosol generated with an atomizer that contains the product to be mixed together with the encapsulant.
• industrial equipment consists of a feed system for the solution to be atomized, an atomizer, high temperature drying chamber and microparticle collector. In these cases the collector can be a cyclone, cartridge, etc. collector.
• the technical problem of spray drying is that it is limited to working with stable products since the high temperature used (generally above 100 ° C) degrades labile products. Lyophilization is a process that involves freezing at low temperatures (-80 ° C) followed by sublimation of the solvents by applying vacuum. This technique does allow working with labile products but it is necessary to use suitable cryoprotective agents.
• a similar technique in which a fluid field is used instead of an electric field to obtain greater control of the generated jet, and therefore of the size of drops and microparticles, is the technique of focused flow (flow focusing). With it, greater control of the microparticle size is obtained than with conventional nebulizers. It consists of an injector, usually a tube, where the working solution is injected and a coaxial air flow that reduces the size of the solution jet, allowing drop size control and therefore of the generated microparticles. The reduced droplet size generated by this technique facilitates drying at room temperature, maintaining the viability of labile products.
• Patent document US20120263826A1 describes a drinkable product comprising at least one aqueous liquid and capsules comprising probiotic bacteria trapped between them Lactobacillus Rhamnosus. Some probiotic encapsulation techniques that can be used and their disadvantages are also described.
• WO02060275 it describes a process of producing capsules or particles of micro and nanometric size using stable electrified coaxial jets of at least two immiscible liquids, for example, a first liquid that is surrounded by a second liquid, where the second liquid provides a barrier or protective coating.
• the process can be carried out under a dielectric atmosphere of, preferably an inert or empty gas atmosphere.
• the present invention proposes an industrial drying and / or encapsulation installation of thermolabile substances. It also describes a drying process with industrial encapsulation of thermolabile substances that allows to overcome the described drawbacks of the prior art solutions.
• This invention allows the generation of micro, submicro and nanoparticles in the case of their use for drying or of micro, submicro and nanocapsules in the case of their use for encapsulation.
• microcapsules are referred to as this is the size obtained in the specific examples shown.
• thermolabile substances can be encapsulated, for example, to facilitate and homogenize the dosage of the product, to mask flavors, to protect the product inside the microcapsule, generally from humidity, light and ambient oxygen, to achieve a controlled discharge of the active component that remains inside the microcapsule or to increase its bioavailability.
• Thermolabile substance means that substance that needs to be coated to maintain its stability.
• examples of such substances in the present invention are microorganisms, enzymes, polyunsaturated fatty acids, antioxidants, vitamins, essential elements or any molecule or derivative compound.
• Examples of these means would be encapsulation of essential oils or enzymes in various matrices including natural matrices such as zein, whey protein and pululane or synthetic such as PEO (polyethylene oxide) or PVP (polyvinylpyrrolidone).
• natural matrices such as zein, whey protein and pululane or synthetic such as PEO (polyethylene oxide) or PVP (polyvinylpyrrolidone).
• An object of the invention is the installation of industrial drying and / or encapsulation of thermolabile substances comprising: - an injection equipment, which is preferably a nebulizer or an electrospray, - a drying equipment, which is arranged next to the injection equipment, and
• the installation allows to obtain industrial quantities of microcapsules of thermolabile material at a controlled temperature maintaining or increasing the protection (protection of the content of thermolabile material inside the microcapsule) that provide other low production techniques, such as electrospray and flow focusing .
• the injection equipment comprises an injector at the entrance of which a solution comprising the thermolabile substance to be encapsulated, the encapsulating material, a solvent and necessary additives is introduced.
• a solution comprising the thermolabile substance to be encapsulated, the encapsulating material, a solvent and necessary additives is introduced.
• a solution mixture of liquids or miscible solid liquids
• an emulsion mixture of non-miscible liquids
• a suspension mixture of solids insoluble in liquid
• the injection equipment projects microdroplets whose size can be focused and controlled more efficiently by applying an electric field to the outlet of the injector (in this embodiment the injection equipment can be an electrospray).
• the injection equipment comprises a typically circular electrode, which is placed at the outlet of the injector.
• the solution is electrically charged during the atomization, when said electric field is generated by applying high voltage, both in alternating current (AC) and in direct current (DC). Adding the electric field allows you to better control the size and monodispersity of sizes of the micro drops that are generated in the injection equipment. As thermolabile substances are to be encapsulated and hot air is not going to be applied for drying, the micro-drops generated must be very small to reduce subsequent drying times.
• the injection equipment comprises a nebulizer, atomizer or aerosol type injector, including pneumatic, piezoelectric, ultrasonic, vibratory devices, etc.
• the injection equipment comprises a pneumatic nebulizer of the type comprising an inlet for a liquid solution and two inlets for injection gas.
• the injection equipment comprises two injection gas inlets of which an injection gas inlet is arranged coaxial to the solution inlet and an additional injection gas inlet is arranged with some inclination with respect to the inlet of dissolution.
• one of the injection gas inlets is arranged so that the injection gas flow is projected in a coaxial direction to the dissolution flow, as in any nebulizer, and the other inlet is arranged so that the gas flow injection is projected at a certain angle to the solution flow, impacting the liquid flow jet.
• a gas flow can be air, nitrogen or other gas and mixtures thereof.
• an inert gas would be used to work in a protective atmosphere or when a flammable solvent is used.
• the injection equipment projects microdroplets whose size depends on the type of injector, specifically in the preferred case where the injection equipment comprises a nebulizer as described, the size depends on the flow rate of a dissolution stream, of the flow of an injection gas stream, and of the properties of the solution, mainly surface tension, conductivity and viscosity. Additionally, the present invention proposes the use of an external electric field to have greater control of the size of the microdroplets and their monodispersity.
• the injection equipment comprises a typically circular electrode that is placed just at the outlet of the injector. The liquid, during the atomization, is charged electrically when passing through said electrode, which is working at high voltage, both in direct and alternating current.
• the drying equipment temperature controlled drying of the micro drops formed in the injection equipment is carried out.
• the solvent of the solution with which the microcapsules have been formed evaporates.
• the solvent evaporates completely giving rise to the desired microcapsules that are subsequently collected in the collection equipment.
• the equipment can dry and encapsulate at a controlled temperature, typically at room or sub-ambient temperature, without the need to apply high temperature heat to vaporize the solvent.
• thermolabile substances are used at room temperature
• the installation and the procedure allow working at sub-ambient temperature, such as at 5 ° C.
• the drying equipment comprises a receptacle. At one end of said receptacle are the injection equipment and a drying gas inlet. At the opposite end is the collection equipment.
• the drying gas is introduced into the temperature controlled drying equipment.
• the drying gas may be air, nitrogen or other gas and mixtures thereof.
• the arrangement of the drying equipment with respect to the injection equipment can be both coaxial with it and with any angle of inclination between them.
• the present invention preferably proposes a coaxial arrangement.
• the drying gas is introduced into the drying equipment at controlled temperature, typically at room temperature.
• the drying gas As the drying gas is introduced into the drying equipment in a certain direction, it carries with it the micro-drops generated in the injection equipment. During the journey through the drying equipment, the solvent in the micro-drops evaporates, thus giving rise to the desired microcapsules.
• the geometry of the a priori drying device can be any that allows a suitable residence time for drying the drops.
• An optimal geometry would be a cylinder with variable circular section, with increasing section from the entrance to the exit. This allows to generate a greater drag in the zone in which the drops are of greater size and this allows the greater time of residence for a given length.
• the installation comprises a drying device comprising a secondary inlet, arranged perpendicular to its longitudinal axis.
• Drying equipment comprises a jacket and a secondary gas flow.
• This secondary gas flow is injected perpendicular to the surface of the drying equipment through holes or pores arranged on the surface of the drying equipment. This allows a reduction of the loss of material by adhesion on the walls of the drying equipment.
• the secondary gas may be air, nitrogen or other gas and mixtures thereof.
• the flow of drying gas must be sufficient to be able to absorb all the solvent that is injected from the injection equipment.
• the maximum amount of water that the flow of drying gas can absorb is less when the relative humidity of the drying gas used is higher.
• a smaller section size of the drying equipment is selected, which generally has a cylindrical configuration, when it is desired to achieve greater drag and collection of the microcapsules. This is due to the fact that if the flow of drying gas is maintained, and the section of the drying equipment is reduced, the drag speed inside the drying equipment increases.
• higher gas speeds obtained, for example, by decreasing the size of the drying equipment section as previously explained
• the installation will be designed maintaining compromising dimensions to optimize drag speed and drying time depending on the solution used for encapsulation.
• the drying time is also called residence time as reference is made to the time during which the microdrops remain in the drying equipment.
• the design of the drying equipment depends on the solvent used and the thermolabile substance to be encapsulated since both factors strongly influence the droplet size generated by the injection equipment and the evaporation kinetics of the latter.
• the optimal diameters and lengths of the drying equipment that allow optimum speeds and residence times for, for example, an installation with a manufacturing efficiency of approx. 1 kg / h of dried or encapsulated product are typically and without limitation between 2 and 200 cm in diameter and between 20 cm and 20 meters in length respectively. Larger industrial facilities could make use of predictably larger diameters and lengths.
• the proposed installation is therefore optimal for industrial use because of its high performance and allows the procedure to obtain microcapsules of thermolabile substances in continuous and in a single step.
• the installation more specifically the drying equipment, can operate at different pressures, even under vacuum.
• the collection equipment allows to efficiently separate the microcapsules generated from the drying gas.
• the collection equipment may comprise at least one cyclonic separation device, centrifugal separation or filtration device, with or without electrostatic charge.
• the collection equipment is a cartridge filter manifold or a cyclone collector.
• the collection equipment comprises a cyclone collector and a cartridge filter placed in series. This allows the larger microcapsules to be collected in the cyclone collector and the smaller ones in the cartridge filter manifold.
• inert gases typically nitrogen
• ATEX category comprising venting and suppression devices.
• the injection gas and the drying gas must be filtered, typically by passing them through a hepa H14 or similar filter, or sterilized, typically by exposure in ultraviolet light, ethylene oxide, irradiation, etc. or combination of both.
• both the preparation of the solution and the handling of the collected product are carried out in a sterile white room or similar installation.
• the collection equipment comprises a solvent condensate device, arranged at the outlet of the drying gas, downstream of the collection equipment.
• the drying gas that is collected at said drying gas outlet is recirculated to feed back the injection equipment and / or the drying equipment.
• the recovery of the solvent or its closed-loop feedback is of special interest when the solvent or drying gas used is of high cost or for reasons of safety or sterility.
• the installation may also include a pre-drying device for the incoming gas to facilitate drying of the microdroplets or their recirculation in a closed circuit. This case is a preferred embodiment when the drying gas is ambient air.
• thermolabile substances which is carried out in an installation as previously described is also an object of the invention.
• Said process comprises at least one step of preparing a polymer solution comprising a thermo-labile substance to be encapsulated, an encapsulating precursor, and an organic or aqueous solvent preferably selected from ethanol, isopropanol, water and a combination thereof.
• the process also comprises a step of forming microdroplets from the polymer solution previously obtained, in the presence of an injection gas flow.
• the process comprises a step of drying the micro-drops obtained in the drying equipment at a controlled temperature and a step of collecting the corresponding microcapsules obtained after drying by means of the collection equipment.
• Figure 1a Shows an example of the installation for the installation drying and / or industrial encapsulation of thermolabile substances where the injection equipment (1), the drying equipment (2) and the collection equipment (3) are appreciated.
• Figure 1b It shows another embodiment of the installation for drying and / or industrial encapsulation of thermolabile substances comprising an electrical circuit (9) arranged in the microdroplets outlet (14) of the injection equipment (1).
• Figures 2a-2d They show SEM micrographs and graphs of particle sizes obtained for an embodiment example in which Omega3 is encapsulated in an installation whose injection equipment is a nebulizer and in which zein encapsulant precursor has been used and pululano.
• Figure 3. Shows a comparative study normalized to 1 of viability obtained by infrared spectroscopy in KBr pellets transmission of the microcapsules and of the uncapsulated Omega3 obtained according to the examples represented in figures 2a-2d.
• Figures 4a-4h. They show SEM micrographs and graphs of particle sizes obtained for an example of embodiment in which Omega3 is encapsulated in an installation whose injection equipment is an electrospray and in which ethanol has been used as solvent 70 % and as a zein encapsulant precursor.
• Figures 5a-5h. They show SEM micrographs and graphs of particle sizes obtained for an example of embodiment in which Omega3 is encapsulated in an installation whose injection equipment is an electrospray and in which water has been used as solvent, as a pululane encapsulation material and as a Tego® surfactant.
• Figures 6a-6f.- They show SEM micrographs and graphs of particle sizes obtained through different existing commercial procedures for the encapsulated Omega3.
• Figures 7a-7b.- They show an SEM micrograph and a graph of particle sizes obtained for encapsulation of Lactobacillus Rhamnosus in an installation in which the injection equipment is a nebulizer.
• Figures 8a-8h. They show SEM micrographs and graphs of particle sizes obtained for an embodiment example in which Lactobacillus Rhamnosus is encapsulated in an installation whose injection equipment is an electronebulizer and in which it has been used as an encapsulating precursor whey protein, as Tego® surfactant and as whole milk liquid matrix.
• Figure 9. It shows a feasibility study in which a comparison between the Lactobacillus Rhamnosus microparticles obtained by lyophilization according to standard procedure using maltodextrin as cryoprotectant and the microcapsules obtained by the procedure and installation described when the injection equipment is a nebulizer and when it is an electrospray.
• thermolabile substances referring to a manufacturing scale of 1 kg / h of dried or encapsulated product. It is expected that facilities that generate a greater volume of production may require higher and scalable installation and processing parameters than those described and therefore the proposed parameters should not be considered as limiting. Likewise, some examples of the realization of industrial encapsulation procedures for thermolabile substances in the proposed installation are described.
• the installation comprises, as shown in Figure 1, at least:
• an injection equipment (1) comprising at least one injector with at least one inlet for a solution (6) (in which the thermo-labile substance to be encapsulated, the encapsulating material in case it is used for a encapsulation process, a solvent and necessary additives), an inlet for the gas from injection (8), and an outlet of microdroplets (14) for the solution that is sprayed into microdroplets;
• a drying equipment (2) arranged next to the injection equipment (1) and comprising at least one inlet for drying gas (7) and an inlet for the microdroplets (1 1) leaving the injection equipment (1 ); and comprising a longitudinal receptacle (12), which preferably has a cylindrical configuration, and which is arranged with its longitudinal direction horizontally and that is of sufficient length to allow evaporation of the entire solvent from the microdroplets; and it has an outlet of microcapsules and drying gas (13) through which microcapsules pass (which are the microdrops already without the solvent, which has evaporated along the path through the drying equipment);
• the collection equipment further comprises a solvent condensate device (10), arranged at the outlet of the drying gas (5), downstream of the collection equipment (3).
• the installation may comprise a drying gas recirculation device that allows the drying gas to be redirected towards the injection equipment (1) and / or the drying equipment (2).
• the injection equipment injector is a nebulizer consisting of an atomizer as described above.
• the injection gas flow rate is, in one embodiment, between 1 and 500LPM.
• the flow of injected liquid which can be found in solution, emulsion or suspension, is preferably between 1 ml / h and 50 lJh.
• the installation additionally comprises a high voltage electrical circuit (9) at the outlet of the injection equipment (1).
• the voltage used in the circuit depends on the solution flow injected and varies between 100V and 500kV. The effect that is achieved is to load the solution, focus the microdrops beam and collaborate in the formation of the microdroplets, improving their size control.
• a high monodispersity can be essential for the final product since it allows greater homogeneity in the protection or release of the thermo-labile material that has been encapsulated and therefore greater control of the encapsulation process.
• the flow of drying gas is between 10 and 100,000 m 3 / h.
• drying is more complex because the drying gas is humidified and therefore it takes more time to remove the water from the solution in the drying equipment.
• the installation may additionally comprise a drying gas pre-drying device so that said drying gas that is introduced into the drying equipment is drier and thus increase the installation efficiency.
• a drying gas pre-drying device so that said drying gas that is introduced into the drying equipment is drier and thus increase the installation efficiency.
• drying is easier because the drying gas, typically air, does not bring solvent.
• the drying gas is free of ethanol and therefore this does not affect the evaporation rate of the ethanol in the drying equipment.
• the drying equipment additionally comprises, in an exemplary embodiment, a pressure control device that allows working at different pressures, even under vacuum.
• the installation is designed to obtain a microcapsule size of 1 to 50 micrometers in diameter.
• the optimal diameters and lengths of the drying equipment are between 20 and 200cm in diameter and between 20 cm and 20 meters in length.
• the drying equipment comprises a cylindrical receptacle 60 centimeters in diameter and 2 meters in length with conical inlet and outlet.
• An object of the present invention is also an industrial encapsulation process of thermolabile substances that is carried out in the previously described installation. This procedure includes the following stages:
• an aqueous or organic solvent which will preferably be selected from ethanol, isopropanol, water and a combination thereof, and
• step (b) forming microdroplets from the polymer solution obtained in step (a) in the presence of an injection gas flow;
• step (b) drying the microdroplets obtained in step (b) in the drying equipment at room temperature and using an air flow rate between 10 m 3 / h and 100,000 m 3 / h to obtain microcapsules;
• step (c) collect the microcapsules obtained in step (c) through the collection equipment.
• the polymer solution of step (a) may be a solution as such, that is to say a mixture of liquids or a mixture of liquids and miscible solid solids; an emulsion, that is, a mixture of non-miscible liquids; or a suspension, that is, a mixture of solids insoluble in liquid.
• the encapsulating precursor of step (a) is selected from animal, vegetable and microbial proteins. More preferably, the encapsulating precursor of step (a) is selected from whey, caseins, natural polypeptides or obtained by genetic modification of microorganisms, collagen, soy protein and zein. Even more preferably, the encapsulating precursor of step (a) is selected from zein and whey protein.
• the encapsulating precursor of step (a) are oligosaccharides selected from lactose, sucrose, maltose and fructooligosaccharides. More preferably, the encapsulating precursor of step (a) is a fructooligosaccharide.
• the encapsulating precursor of step (a) are polysaccharides selected from alginate, galactomannan, pectins. Chitosan, gums, carrageenans, pululane, fucopol, starch, dextran, maltrodextrin, cellulose, glycogen and chitin. More preferably, the encapsulating precursor of step (a) is selected from pululane, dextran, maltodextrin, starch and any combination. thereof.
• additives will be used to optimize the properties of the solution.
• additive is understood as that substance selected from a plasticizer, surfactant, emulsifier, surfactant, antioxidants or any combination thereof.
• examples of additives in the present invention would be commercially known as Tween®, Span®, and Tego® surctactants, more preferably Tego®, for use in food is permitted.
• step b) of micro droplet formation is performed by applying a voltage between 0.1 kV and 500 kV to the solution flow and injection gas at the outlet of the injection equipment. More preferably step b) of microdrops formation is performed by applying a voltage between 5 kV and 60 kV to the solution flow and injection gas at the outlet of the injection equipment. Preferably the applied voltage is between SkV and 15kV.
• step b) of micro droplet formation is performed by applying an alternating current voltage.
• the injection gas flow rate in step (b) is between 1 and 500LPM.
• step (c) drying gas flow rates of between 10 m 3 / h and 100.00 m 3 / h are used to obtain microcapsules of 1 to 20 micrometers in diameter.
• thermolabile compounds to be protected are preferably microorganisms, antioxidants, viruses, enzymes, polyunsaturated fatty acids, essential elements or any molecule or derivative compound.
• thermolabile compounds are selected from the group consisting of antioxidants (vitamin C, vitamin E, carotenoids, phenolic compounds such as flavonoids and resveratrol) and concentrates or isolates of natural or synthetic antioxidants, biological organisms such as valuable cells in biomedicine and probiotics (such as Lactobacillus and Bifidobacterium), other microorganisms such as Cyanobacter ⁇ um, Rhodobacterales and Saccharomyces, prebiotics (lactulose, galacto-oligosaccharides, fructo-oligosaccharides, malto-oligosaccharides, xylo-oligosaccharides and soy oligosaccharides), symbiotics, functional fibers, oleic acid, polyunsaturated fatty acids (omega-3 and omega-6) and other marine oils , phytosterols, phytoestrogens, ingredients of a protein nature (AON and its derivatives, lactoferrin
• thermolabile compounds will be selected from the group consisting of:
• thermolabile substances to be encapsulated are OmegaS and probiotics.
• the probiotic selected has been Lactobacillus Rhamnosus.
• Examples 1.1 and 1.2 describe non-limiting procedures for encapsulating Omega3 oil and the corresponding feasibility studies are described.
• Example 1.1 Encapsulation of Omeaa3 using a nebulizer as an injector
• a conventional nebulizer has been used as injection equipment.
• different candidate natural polymers are used to encapsulate Omega3 oil and thus prevent its oxidation and the transmission of odors and flavors to food in direct contact, such as zein, pululane, whey protein, and modified maltodextrins ( Pineflow® and Nutrióse®).
• the capsules generated with the highest potential materials, zein and pululane can be seen in the SEM micrographs of Figures 2a and 2b respectively.
• Figures 2c and 2d show the optimal sizes, in the range of 2-10 microns, in a size distribution graph, corresponding respectively to the micrographs of Figures 2a and 2b.
• the experimental parameters and ranges of use are shown in tables 1 and 2 respectively.
• Table 1 Experimental parameters and operating ranges of the procedure of Example 1.1 using zein.
• Table 2 Experimental parameters and operating ranges of the processing of Example 1.1 using pululane.
• FIG. 4a-4d show the effect of the technical field on the geometry of the microcapsules. More specifically in said figures the microcapsules are shown when no electric field is applied (figure 4a), when the electric field is 1 kV (figure 4b), when the electric field is 5kV (figure 4c) and when the electric field is 10kV (figure 4d).
• an optimized electric field allows greater control over the geometry of the microcapsule, allowing geometries of great sphericity, high monodispersity and size control.
• Table 4 Experimental parameters and operating ranges of the processing of Example 1.2 using a solution comprising water, pululane and Tego®.
• Figures 6a-6f show SEM micrographs and corresponding particle size distribution for different procedures for obtaining existing commercial microcapsules.
• Figures 6a-6d show results obtained with procedures known in the state of the art. More specifically, in figure 6a the results obtained with BASF (spray-drying with nitrogen atmosphere) have been represented, in figure 6b the results obtained with LIFE (air spray-drying) are shown, in figure 6c they are shown the results obtained with MEG (spray-drying in air) and in figure 6d the results obtained with STEPAN (spray-drying with nitrogen atmosphere) are shown.
• Figures 6e and 6f The results obtained with the process of the present invention are shown in Figures 6e and 6f ( Figure 6e shows the results obtained when the procedure is performed in an installation in which the injection equipment is a nebulizer and in the figure 6f shows the results obtained when the procedure is performed in an installation where the injection equipment is an electrospray).
• Figure 6e shows the results obtained when the procedure is performed in an installation in which the injection equipment is a nebulizer
• figure 6f shows the results obtained when the procedure is performed in an installation where the injection equipment is an electrospray.
• table 5 shows a tasting study conducted by mixing a fixed amount of Omega3 microcapsules with powdered milk and water.
• a mixture of powdered milk and water has been used and the nomenclature followed to assess the tasting has been:
• Examples 2.1 and 2.2 describe non-limiting procedures for encapsulating Lactobacillus Rhamnosus probiotics and the corresponding feasibility studies are described.
• Example 2.1 Encapsulation of a probiotic using a nebulizer as an injector
• a nebulizer and, as a polymer to encapsulate the probiotic, whey protein has been used as an injection equipment.
• Figure 7a shows an SEM micrograph showing the microcapsules obtained and
• Figure 7b shows a graph with the distribution of sizes obtained.
• Table 6 shows the experimental parameters and the ranges of use of this example.
• Table 6 Experimental parameters and operating ranges of the processing of Example 2.1 using a solution comprising milk soil protein, Tego® and whole milk.
• Example 2.2 Encapsulation of a probiotic using an electrospray as an injector
• an electrospray and the same natural polymer as in example 2.1 have been used as the injection equipment.
• Figures 8a-8d show SEM micrographs of the microcapsules obtained by applying different electric current values (more specifically without applying electric current, applying 1 kV, 5kV and 10kV respectively).
• the size value of the microcapsules obtained in these cases has been represented in Figures 8e-8h. Table 7 shows the experimental parameters and the ranges of use of this example.
• Figure 8 shows the effect of the addition of the bacteria on the sizes of the microcapsules.
• Table 7 Experimental parameters and operating ranges of the processing of Example 2.2 using a solution comprising milk soil protein, Tego® and whole milk, without using electric current and using an electric current of 10kV.
• both the electrospray encapsulation and the nebulizer encapsulation show better results than those obtained by the known freeze drying technique which is what has been represented as a reference technique.

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